The purpose of the proposed research is to further delineate the neural substrates of cocaine dependence. Characterization of the neural substrates of cocaine reinforcement and withdrawal will provide information critical to the prevention, treatment and medication of cocaine abuse and drug abuse in general. The nucleus accumbens, a forebrain region innervated by mesolimbic dopamine neurons, has been strongly implicated in cocaine reinforcement. Recent anatomical evidence has linked the nucleus accumbens to two forebrain nuclei which are both innervated by mesolimbic dopamine neurons, the amygdaloid central nucleus (Ace) and the dorsolateral bed nucleus of the stria terminalis (dlBNST). In addition, the potential roles of corticotropin releasing factor (CRF) and neuropeptide Y (NPY) in the Ace and d1BNST in cocaine reinforcement and withdrawal will be investigated. Specific Aim 1 will test the effects of antagonists of dopamine (selective for D1, D2, and D3 receptors), CRF and NPY injected into the Ace and dlBNST on cocaine self-administration in rats. Specific Aim 2 will test the effects of injections of antagonists of dopamine, CRF and NPY into the Ace and d1BNST on the elevations in intracranial self-stimulation thresholds observed during cocaine withdrawal in rats. These studies will go far toward the characterization of the neural substrates of cocaine abuse and dependence.